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Volume 137, Issue 6 , Pages 1356-1362.e3 , June 2009

Myocyte apoptosis occurs early during the development of pressure-overload hypertrophy in infant myocardium

Yeong-Hoon Choi, MD
- Department of Anesthesiology and Perioperative and Pain Medicine, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
- Department of Cardiac Surgery, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
- Anesthesia/Critical Care Medicine Research Laboratory, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
- Address for reprints: Yeong-Hoon Choi, MD, Children's Hospital Boston and Harvard Medical School, Department of Cardiac Surgery, 300 Longwood Avenue, Boston, MA 02115. Current address: Heartcenter of the University of Cologne, Department of Cardiothoracic Surgery and Center of Molecular Medicine Cologne, Kerpener Str 62, 50924 Cologne, Germany.
Douglas B. Cowan, PhD
- Department of Anesthesiology and Perioperative and Pain Medicine, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
- Anesthesia/Critical Care Medicine Research Laboratory, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
Adrian M. Moran, MBBS
- Department of Cardiology, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
Steven D. Colan, MD
- Department of Cardiology, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
Christof Stamm, MD
- Department of Cardiac Surgery, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
Koh Takeuchi, MD
- Department of Cardiac Surgery, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
Ingeborg Friehs, MD
- Department of Cardiac Surgery, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
Pedro J. del Nido, MD
- Department of Cardiac Surgery, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
Francis X. McGowan Jr., MD
- Department of Anesthesiology and Perioperative and Pain Medicine, Children's Hospital Boston, and Harvard Medical School, Boston, Mass
- Anesthesia/Critical Care Medicine Research Laboratory, Children's Hospital Boston, and Harvard Medical School, Boston, Mass

Received 1 July 2008 ,Revised 20 November 2008 ,Accepted 22 December 2008.

Effects of aortic banding of infant rabbits on LV mass:volume ratio determined by serial echocardiography. Data are mean ± standard deviation (SD), n = 6–10 each. #P < .05 versus age-matched controls.

Effects of aortic banding of infant rabbits on LV mass:volume ratio determined by serial echocardiography. Data are mean ± standard deviation (SD), n = 6–10 each. #P < .05 versus age-matched controls. ^∗P < .05 versus 4-week-old banded. LV mass:volume ratio increases early in hypertrophy and then progressively declines. LV, Left ventricular.
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Effects of aortic banding of infant rabbits on LV peak systolic stress. Data are mean ± SD, n = 6–10 each. Peak systolic stress is reduced in banded animals at 4 weeks in association with increased LV

Effects of aortic banding of infant rabbits on LV peak systolic stress. Data are mean ± SD, n = 6–10 each. Peak systolic stress is reduced in banded animals at 4 weeks in association with increased LV mass (see Figure 1). Failure of continued hypertrophy in the face of increasing afterload results in a progressive increase in peak systolic stress. ^∗P < .05 versus controls. PkSS, Peak systolic stress.
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Apoptosis in LV myocardium of control sham-operated and banded infant rabbits. A, Representative fluorescent photomicrographs of 5-μm sections of the LV wall from banded rabbits. Sections were labeled

Apoptosis in LV myocardium of control sham-operated and banded infant rabbits. A, Representative fluorescent photomicrographs of 5-μm sections of the LV wall from banded rabbits. Sections were labeled with Hoechst to stain nuclear DNA (blue), desmin to identify cardiomyocytes (red), and DNA strand breaks (TUNEL-green). After image acquisition, images were subjected to 2-dimensional “no neighbors” deconvolution using a kernel that estimates the 3-dimensional point spread function based on the optics and imaging system. A and B, Banded animal at 3 weeks. C and D, Banded animal at 7 weeks. Apoptotic nuclei localized to myocytes (arrows); TUNEL-positive staining in non-myocytes (asterisks). B, Assessment of myocyte apoptosis in sham versus banded animals using this approach. Data are mean ± SD, n = 6–8 each. The difference between sham-operated and banded animals was significant at all ages.
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LV myocardial caspase-3 activity measured by cleavage of the specific fluorescent substrate DEVD-AFC (BioMol, Plymouth Meeting, Pa) in age-matched sham operated control (open bars) and banded hypertro

LV myocardial caspase-3 activity measured by cleavage of the specific fluorescent substrate DEVD-AFC (BioMol, Plymouth Meeting, Pa) in age-matched sham operated control (open bars) and banded hypertrophying (solid bars) hearts. Data are mean ± SD, n = 5–7 per group and expressed as arbitrary fluorescent units relative to that measured in 7-week controls. ^∗P = .04. #P = .03. +P = .008.
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